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Carolina Gabay
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P21 - Locoregional and Oligometastatic Disease - Treatment of Locally Advanced NSCLC (ID 131)
- Event: WCLC 2020
- Type: Posters
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P21.13 - Durvalumab in Locally-Advanced NSCLC in LATAM: Real World Data from Patients Included in the Early Access Program (ID 3051)
00:00 - 00:00 | Author(s): Carolina Gabay
- Abstract
Introduction
Most patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) have disease progression after definitive chemoradiotherapy. The phase III PACIFIC trial comparing durvalumab versus placebo after chemoradiotherapy lead to the approval of durvalumab as a new standard of care for patients with unresectable stage III disease. Durvalumab improved progression-free survival (PFS) vs placebo and overall survival (OS) [13.5% absolute benefit at 36-month overall survival rate].
We present disease characteristics from patients included in the Early Access Program (EAP) in Argentina and Chile.
Methods
The EAP opened in Argentina and Chile in December 2017 and October 2018, respectively. Key inclusion criteria were adults with locally advanced, unresectable stage III NSCLC (according to 7th edition of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) who have completed treatment with platinum-based chemotherapy concurrently or sequentially with radiation therapy, without evidence of disease progression within 3 months from the end of radiation and have adequate organ and marrow function. Patients received durvalumab 10 mg/kg every 2 weeks up to 12 months or until disease progression, toxicity or withdrawal of consent.
Results
Argentina and Chile enrolled 44 patients from 16 centers, both private and public health care centers. Median follow-up was 20.2 months (range 6.5-37.3). The median age was 66 years (42-79); 22 (50%) were females; 27 (61,4%) former smokers and 29 (66%) had ECOG 0. Thirty (68.2%) were non-squamous histology. Nineteen (43.2%) were staged with mediastinoscopy, 4 (9.1%) with EBUS, 3 (6.8%) had a videothoracoscopy and 18 (40.9%) were considered clinically as locally advanced disease. Twelve (27,3%) patients were stage IIIA and 32 (72.7%) IIIB. Forty (90,9%) had received concurrent chemoradiotherapy (ChRT), with platinum-pemetrexed 22 (52.3%) and weekly carboplatin-paclitaxel 19 (43.2%). All patients completed planned radiotherapy; 30 (68.2%) received 60Gy (45-66). Median time for first CT scan after ChRT was 34 days (range 0-144). Twenty-seven (61,4%) had partial response after ChRT and one had disease progression. Thirty-three (75%) patients had PD-L1 testing, 8 with >25%. One patient had EGFR mutation. At data cut-off (July 8 2020), 41 patients had started treatment, 4 (9.7%) were still on-going, 15 (36.5%) had completed treatment and 32 (78%) were alive. Median time to initiation of durvalumab was 82 days (range 19-260) from the end of RT. Median cycles of durvalumab 15 (range 2-26). Twenty-one (51.2%) had disease progression during treatment. Main sites of progression were lung, lymph nodes and CNS. After progression, 13 (31.7%) patients received other treatment (24.4% chemotherapy (ChT), 4.9% ChT and IO, 2.4% EGFR TKI). Thirty-three (80,5%) patients had grade 1-2 toxicities (asthenia, hypothyroidism, diarrhea and pneumonitis). One patient discontinued treatment due to grade 3 (G3) pneumonitis and one had G3 increase in transaminases. No grade 4/5 adverse events were reported.
Conclusion
The use of durvalumab in patients with locally-advanced unresectable stage III NSCLC in a real-word setting in two LATAM countries was well tolerated. Most of the patients completed concurrent ChRT, both private and public setting. Efficacy data is still immature and will be presented in subsequent analysis
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.12 - A Meta-Analysis of ICI +EP vs. EP for Untreated Extensive SCLC using GRADE System Approach for Certainty in the Evidence. (ID 2950)
00:00 - 00:00 | Presenting Author(s): Carolina Gabay
- Abstract
Introduction
Etoposide plus platin (EP) have been the standard of care for treating extensive SCLC. Adding Immune CheckPoint inhibitors (ICI) has emerged as a new strategy; however, the magnitude of clinical benefit remains controversial for their use.
We conducted a critical appraisal using a partially contextualized GRADE ( Grading of Recommendations, Assessment, Development and Evaluations) approach.
Methods
Following PRISMA guidelines, a comprehensive systematic review was performed from 2014 to June 2020. We included randomized controlled trials (RCT) comparing ICI plus EP vs. EP in the first-line setting. The main outcomes were OS, PFS, safety, and QOL.
A meta-analysis was conducted using the random and fixed effects models provided by Review Manager (version 5.3). The heterogeneity of the pooled estimates was considered using I2 statistical. The risk of bias (ROB) was assessed with the Cochrane ROB Tool.
Then , we usedGRADEpro® for judging and rating the certainty in the estimates of effectconsidering 5 domains: ROB, precision, consistency, directness, and publication bias for each outcome.
Results
Of the 387 records identified, 4 RCT met the eligibility criteria. In 3 the main measure was OS; 1 was a phase II;2 was phase III, and 3 were funded by a pharmaceutical sponsor.
N= 1553 pts were included in this meta-analysis. The pooled HR for OS and PFS were 0.75 (95% CI 0.55-0.84) and 0.76 (0.68-0.85), with anticipated absolute effects of 101/1000 less (147-60) and 70/1000 fewer (103-39) events respectively. In the CNS metastatic subgroup, the HR for OS was 1.08 (0.75-1.55) (N = 144, 3 RCTs, 1RCT not reported) .
The RR for AEs G≥3 was 1.03 (0.96 to 1.11). The RR for immunomediated AEs (3 RCTs, N = 1371, median number of cycles=7) was 2.39 (1.88, 3.02; I2 = 87%) and 1.88 (1.46, 2.41; I2 = 49%) when blinded RCTswere considered.
ROB was classified as not serious for OS but was defined as serious for PFS, ORR; and safety outcomes because of the open nature of 2 RCTs without adequate strategies to minimize bias.
Inconsistency was found in immune-mediated AEs related to an unexplained heterogeneity (I2 = 87%) between trials.
Imprecision was serious for AEs G ≥3, and CNS metastatic subgroup (3 RCTs,N=123) because the pooled estimates with their 95% CI include both benefit and harm for the intervention of interest (overlapping with the threshold for no effect).No publication bias was detected.
No QOL data related to the selected RCTs was found.
Conclusion
The certainty of evidence was high for OS (critical outcome), moderate for PFS, and low for safety results.
The uncertainty about the effectiveness in the CNS metastasis subgroup is an important limitation due to the high frequency of this presentation in the real-world practice.
A threshold that defines clinical impact , the lack of QOL data, and concerns about financial burden are limitations for an adequate decision-making process in this setting.
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P48.16 - Network Meta-Analysis of ICI for Extensive Small-Cell Lung Cancer (ESCLC) as Upfront Therapy (ID 2991)
00:00 - 00:00 | Presenting Author(s): Carolina Gabay
- Abstract
Introduction
Adding ICI to EP is a breakthrough strategy for treating ESCLC in the first-line setting. However, there is no head to head comparison between these agents to guide the clinical decisions.
Thus, we performed a systematic review and network meta-analysis (NMA) to evaluate the effectiveness and safety of ICIs in combination with EP for this target population.
Methods
According to PRISMA-NMA statement , a systematic search of literature was carried out in PUBMED , Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov database up to Jun 31, 2020. Only randomized clinical trials (RCTs) comparing ICIs+EP vs. EP were considered.
We performed an NMA using MetaInsight V 3.13 web-based tool , with a Bayesian framework to estimates risk ratios (RRs) and Odds ratios (OR) with their 95% credible intervals (CrIs). Ranking tables with the probability of best treatment choice for each outcomes , derivated from the model and network estimates were obtained.
OS and PFS rate at 12months , ORR, AEs G3-4 , and immune-related AEs were the selected outcomes.
Results
Five RCTs that involved more than 2000 pts and 7 interventions met the inclusion criteria. All selected trials had EP as a control arm.
No significant differences in the risk of mortality , risk of progression, and risk of immune-related AEs were observed between Atezolizumab (A), Durvalumab+Tremelimumab (DT), Durvalumab (D), Pembrolizumab (P), or Ipilimumab (I) (4 RCTs, n 2615) in association with EP, neither between these interventions and Nivolumab ( 5 RCTs, n 2759) for ORR and EAs G3-4.
In Bayesian ranking results, A and D were most likely to be ranked first for OS (cumulative probability 40%). Meanwhile, P and D were ranked first for ORR (36%) and PFS (30%). In the safety profile, D was ranked with the less probability of AEs G3-4 (30%) , but P and I were first for immune-related AEs (15%).
In the comparison of anti PD-1 vs. PD-L1 agents, therapy with anti PD-1 had the highest chance to provide better ORR (70%) and less immune-related AEs (66%), but anti PDL-1 were best regarding AEs G3-4 (42%) and PFS rate at 12 months (72%).
Due to the comparisons between experimental treatments proceeded only from indirect evidence , inconsistency between direct and indirect estimates was not feasible.
Conclusion
This indirect comparison did not find evidence suggesting survival differences between these agents.
All treatments showed better efficacy results over EP, except A for ORR.
For safety outcomes in PD-1 vs. PD-L1 comparison; even there was a not significant difference in producing AEs G 3-4 or immuno-related AEs, they did not rank similarly. Therefore this distinct pattern of AEs could to be considered for choosing an agent.
Producing data related to the quality of life , economic burden , and patient´s preferences may help to define what would the best option for this population.
